CN109010832A - Pharmaceutical composition containing platelet aggregation inhibitor and vitamine D3 - Google Patents
Pharmaceutical composition containing platelet aggregation inhibitor and vitamine D3 Download PDFInfo
- Publication number
- CN109010832A CN109010832A CN201810824877.0A CN201810824877A CN109010832A CN 109010832 A CN109010832 A CN 109010832A CN 201810824877 A CN201810824877 A CN 201810824877A CN 109010832 A CN109010832 A CN 109010832A
- Authority
- CN
- China
- Prior art keywords
- vitamine
- platelet aggregation
- dosage
- aggregation inhibitor
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The pharmaceutical composition containing platelet aggregation inhibitor and vitamine D3 that the present invention provides a kind of, wherein the dosage of platelet aggregation inhibitor is 50~150mg, and the dosage of vitamine D3 is 200~1500IU.This effect is embodied in the composition other than keeping the existing effect for inhibiting platelet aggregation, moreover it is possible to while the incidence of the bleeding adverse events as caused by platelet aggregation inhibitor is reduced, thus safer and more effective ground antithrombotic.
Description
Technical field
The invention belongs to pharmaceutical fields, specifically, the present invention relates to one kind to contain platelet aggregation inhibitor and Wei Sheng
The pharmaceutical composition of plain D3.
Background technique
A large amount of evidence-based medicine EBMs prove that blood platelet plays an important role in the generation, development of cardiovascular and cerebrovascular disease, uncomfortable
When platelet activation will lead to the generation of atherosclerotic's ischemic event, Antiplatelet therapy is to these clinical diseases
Treatment and prevention have great importance.For thrombus in forming process, acting on blood platelet has multiple links and a variety of drugs,
So clinically having many antiplatelet drugs, such as aspirin, clopidogrel etc., it there may come a time when two kinds of medicines of meeting either
Three antiplatelet drug.But the use of any one existing antiplatelet drug, it all can be along with the increasing of bleeding risk
Add, any antithrombotic treatments are all a double-edged swords, and dosage is too small to be not achieved drug effect, reach drug effect and are just bound to induce
Blood, increases Bleeding rate, and doctor can only be in antiplatelet interests and thus bring bleeding during using such drug
Risk in the careful medication weighed the advantages and disadvantages, therefore how to reduce Bleeding rate caused by antiplatelet drug, become one it is new
Research topic, existing method are to be used together antiplatelet drug with stomach medicine, are such as made in aspirin and clopidogrel
In, in order to reduce by gastrorrhagia caused by drug itself, be added stomach medicine Omeprazole, ranitidine, Hydrotalcite, in gastric acid
With agent etc., but to the local irritation of stomach when these means are only the reduction of administration, or only it is the reduction of the bad thing of stomach
The incidence of feelings can not reduce the incidence of bleeding episode, and these stomach medicines are used for a long time, and also increase stomach medicine itself no
The incidence of good thing, the poultry such as aluminium agent is long-pending, or affects the curative effect of antiplatelet drug.In disclosed document report,
By aspirin be made enteric coatel tablets or and the stomach medicine of gastric acid can be neutralized compound preparation is made, both preparations and common
Tablet paired observation in clinical application, discovery not can reduce the incidence of gastrorrhagia.Therefore find can reduce by
The drug of Bleeding rate caused by antiplatelet drug (such as aspirin) becomes well known to one, and there are no any reasonable solutions
The problem of scheme.
Summary of the invention
The purpose of the present invention is overcome existing antiplatelet drug such as aspirin, clopidogrel, ticagrelor etc. facing
Existing deficiency when applying on bed provides a kind of pharmaceutical composition of more efficiently prevention and treatment thrombotic disease, this effect
Fruit is embodied in the composition other than keeping the existing effect for inhibiting platelet aggregation, moreover it is possible to while reducing by antiplatelet drug
The incidence of bleeding adverse events caused by itself, thus safer and more effective ground antithrombotic.
To achieve the above object, the invention adopts the following technical scheme:
A kind of pharmaceutical composition, comprising: (1) platelet aggregation inhibitor of pharmaceutical dosage；(2) vitamine D3 of pharmaceutical dosage；
(3) the gastric acid buffer of suitable dose selects calcium carbonate and magnesia；(4) acceptable oral carrier in pharmacy.
In composition of the present invention, platelet aggregation inhibitor be respectively clopidogrel, prasugrel, ticagrelor,
Anagrelide, Yi Nuo Gray, dabigatran etcxilate, aspirin, Ah's lapachone (aspalatone), Sarpogrelate, Tiopronin,
Captopril, probucol, Pidotimod and its active metabolite or its pharmaceutically acceptable salt.In the present invention
In, aspirin pharmaceutical dosage is 50~150mg, and clopidogrel pharmaceutical dosage is 50~150mg, and ticagrelor pharmaceutical dosage is
The dosage of 50~150mg, prasugrel and other antiplatelet drugs are according to well known daily conventional consumption per day.Be also possible to
The combination of upper any two kinds of platelet aggregation inhibitor.
In composition of the present invention, vitamine D3 include its active metabolite 25-hydroxyvitamin D3 in vivo and
1-25-(OH)2-D3, also includes the prodrug of vitamine D3, and total pharmaceutical dosage of vitamine D3 is 200-1500IU.
In composition of the present invention, the gastric acid buffer of suitable dose selects calcium carbonate and magnesia.Calcium carbonate its contain
Amount is 500~2500mg, and magnesia is 50~500mg.
Experimental studies have found that, when vitamine D3 and platelet aggregation inhibitor share, platelet aggregation is significantly reduced by this
Collect the adverse reaction of bleeding caused by inhibitor.
The present invention will be further described With reference to embodiment, not limitation of the invention, all according to this
The equivalent replacement of any this field that summary of the invention carries out, all belongs to the scope of protection of the present invention.
Specific embodiment
1. aspirin of embodiment/vitamine D3 and clopidogrel/vitamine D3 and ticagrelor/vitamine D3 are to rat
The influence of capillary of skin permeability.
By weight range at SD rat 42 of 230~280g, back wool is cleared, is only randomly divided into 7 groups by every group 6, point
Not Wei blank group (giving physiological saline), aspirin group (by 30mg/kg gastric infusion, continuous gavage five days), aspirin/
(by aspirin dosage be 30mg/kg to vitamine D3 group and vitamine D3 dosage is 250IU/kg gastric infusion, continuous gavage five
It), clopidogrel group (press 30mg/kg gastric infusion, continuous gavage five days), clopidogrel/vitamine D3 group (press clopidogrel
Dosage is 30mg/kg and vitamine D3 dosage is 250IU/kg gastric infusion, continuous gavage five days), ticagrelor group (presses
30mg/kg gastric infusion, continuous gavage five days), ticagrelor/vitamine D3 (by ticagrelor dosage be 30mg/kg and Wei Sheng
Plain D3 dosage is 250IU/kg gastric infusion, continuous gavage five days).After last time administration 2 hours, rat back is subcutaneously infused
Enter 200 μ g histamine (1mg/ml), immediately the sacrificed by decapitation after tail vein injection 1% Evans blue 0.4ml/100mg, 15min, so
Blue dye skin graft is laid with the 2cm diameter punch of standard afterwards.Rat skin indigo plant dye skin graft is put into 7: 3 acetone and physiological saline is mixed
It closes in liquid (4ml), impregnates in two times, 2 hours every time, merge immersion liquid, in addition stating mixed liquor to 5ml, place electric heating constant temperature sink,
It is incubated for 36 hours at 65 DEG C, until skin blue completely disappears.It is being centrifuged 10min with centrifuge, supernatant is being taken, uses UV, visible light
Light photometric determination absorbance.The results are shown in Table 1, and thus experimental result is it is known that be used alone aspirin, chlorine pyrrole lattice
Thunder and ticagrelor increase capillary permeability, but the addition of vitamine D3, reduce by using aspirin, chlorine
The influence of capillary permeability caused by pyrrole Gray and ticagrelor.
1. aspirin of table/vitamine D3 and clopidogrel/vitamine D3 and ticagrelor/vitamine D3 are to rat skin
The influence (x ± s, n=6) of capillary permeability.
2. aspirin of embodiment/vitamine D3 reduces bleeding gums test.
Select the gerontal patient of long-term (3 years or more) Aspirin (100mg/ days) to amount to 8 people: hepatic and renal function is just
Often；This 8 volunteers are once interrupted and are used wherein 4 patients result in gastrorrhagia or cerebral hemorrhage due to taking aspirin for a long time
Medicine restores medication after (4-8 weeks) again；This 8 patients, have the different degrees of gum as caused by Aspirin to go out
Blood, and influence to live；Gum spy examines bleeding (BOP) rate greater than 60%.It maintains to use aspirin usage and dosage originally in patient
On the basis of constant: guidance wherein 6 patients increase take containing vitamine D3 preparation (600IU/ days, contain one in preparation
Quantitative calcium carbonate), continuous medication six months or more, the bleeding gums situation in medication period is observed, it is found that 6 patient masters state tooth
Oulorrhagia situation improves completely, and gum spy is detected after six months and examines bleeding (BOP) rate less than 30%, the severe haemorrhage of other positions
Situation there is no；Instruct other 2 patients increase take containing vitamine D3 preparation (200IU/ days, contain one in preparation
Quantitative 0.5g calcium), the bleeding gums situation in medication period is observed in continuous medication six months, and two patient masters state bleeding gums
Situation makes moderate progress, and gum spy is detected after six months and examines bleeding (BOP) rate less than 45%, the severe haemorrhage situation of other positions does not have
There is generation.
Claims (10)
1. a kind of pharmaceutical composition containing platelet aggregation inhibitor and vitamine D3.
2. composition according to claim 1, it is characterised in that: the platelet aggregation inhibitor is respectively Ah Si
Woods, clopidogrel and ticagrelor and its active metabolite or its pharmaceutically acceptable salt, and can any two
Person is applied in combination.
3. composition according to claim 1, it is characterised in that: the vitamine D3 is selected from vitamine D3,25- hydroxyl
One of vitamine D3 and 1-25-(OH)2-D3 can also arbitrarily the two be applied in combination.
4. composition according to claim 1, it is characterised in that: material proportion is in composition, Platelet aggregation inhibitor
The dosage of agent is 50~150mg, and the dosage of vitamine D3 is 200~1500IU.
5. composition according to claim 4, it is characterised in that: material proportion is in composition, Platelet aggregation inhibitor
The dosage of agent is 50~100mg, and the dosage of vitamine D3 is 600~1000IU.
6. composition according to claim 2, it is characterised in that: the platelet aggregation inhibitor is aspirin.
7. composition according to claim 2, it is characterised in that: the platelet aggregation inhibitor is clopidogrel.
8. composition according to claim 2, it is characterised in that: the platelet aggregation inhibitor is ticagrelor.
9. according to claim 5 and composition as claimed in claim 6, it is characterised in that: material ratio is in composition, A Si
Woods dosage is 100mg, and the dosage of vitamine D3 is 600~800IU, and the dosage of calcium carbonate is 500~2500mg.
10. composition according to claim 9, it is characterised in that: material proportion is in composition, the dosage of aspirin
For 100mg, the dosage of vitamine D3 is 600IU, and the dosage of calcium carbonate is 1250mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810824877.0A CN109010832A (en) | 2018-07-25 | 2018-07-25 | Pharmaceutical composition containing platelet aggregation inhibitor and vitamine D3 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810824877.0A CN109010832A (en) | 2018-07-25 | 2018-07-25 | Pharmaceutical composition containing platelet aggregation inhibitor and vitamine D3 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109010832A true CN109010832A (en) | 2018-12-18 |
Family
ID=64645846
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810824877.0A Pending CN109010832A (en) | 2018-07-25 | 2018-07-25 | Pharmaceutical composition containing platelet aggregation inhibitor and vitamine D3 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109010832A (en) |
-
2018
- 2018-07-25 CN CN201810824877.0A patent/CN109010832A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2814057C (en) | Intravenous composition comprising paracetamol and ibuprofen | |
| BRPI0513673B1 (en) | METHOD FOR PRODUCTING A MEDICINAL PRODUCT TO INCREASE THE EFFICACY AND TRANSPORT OF BIOLOGICALLY ACTIVE COMPOSITIONS ADMINISTRATED, AND PHARMACEUTICAL COMPOSITION | |
| CN116115551A (en) | Administration of tasimelteon under fasted conditions | |
| JPS62501845A (en) | controlled release potassium chloride | |
| US5397573A (en) | Laxative compositions | |
| Mannis et al. | Ibrutinib rash in a patient with 17p del chronic lymphocytic leukemia. | |
| ES2749752T3 (en) | Orally administrable compositions comprising calcium | |
| JPS5938203B2 (en) | A therapeutic agent for cerebral circulation disorders whose main ingredient is coenzyme Q. | |
| Tsutaoka et al. | Superwarfarin and Glass Ingestion with Prolonged Coagulopathy Requiring High‐Dose Vitamin K1 Therapy | |
| CN109010832A (en) | Pharmaceutical composition containing platelet aggregation inhibitor and vitamine D3 | |
| US20110117070A1 (en) | Compositions and methods for treating headache | |
| US20190000125A1 (en) | Compositions and methods for treating aging and/or improving human health | |
| TW201434464A (en) | A combination medicament comprising phenylephrine and paracetamol | |
| JP2019533672A5 (en) | ||
| WO2016086776A1 (en) | Antifungal compound formulation containing chlorogenic acid and application thereof | |
| US6663896B1 (en) | Delayed release aspirin for vascular obstruction prophylaxis | |
| KR20150143504A (en) | Method and products for enhancing drug and dietary supplement bioavailability | |
| WO2011100668A4 (en) | Methods and compositions of civamide to treat diseases of the intestines | |
| CN102247330B (en) | Sustained release tablet prepared from raw material of safflower yellow and preparation method thereof | |
| RU2146129C1 (en) | Drug | |
| JP2010265186A (en) | Anemia-preventing composition | |
| CN101869567A (en) | Medicament composition containing biguanide antidiabetic medicament and sartan antihypertensive medicament and applications thereof | |
| RU2022134859A (en) | BIS-CHOLINE TETRATHIOMOLYBDATE FOR THE TREATMENT OF WILSON'S DISEASE | |
| Merlob et al. | Gastrointestinal drugs | |
| CN107106602A (en) | Liver fibrosis improver |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20181218 |